Evaluation of the effect of cavitation activity on drug-ultrasound synergisms

The authors investigated the effect of therapeutic ultrasound (1 MHz; 0.5-4 W/cm²) on mammalian cells grown in culture in an exposure system that allowed measurement of sub-harmonic generation. They were able to correlate subharmonic generation in the cell samples, a signature of acoustic cavitation, with cell lysis. Cells exposed to ultrasound demonstrated no membrane damage without detectable subharmonics. In addition, the authors have demonstrated a synergistic (more than additive) effect of ultrasound and several drugs, particularly polar solvents, on cell lysis. The polar solvents dimethylsulfoxide, dimethylformamide (DMF) and monomethylformamide act to significantly enhance cavitation induced cell lysis. In particular, cell lysis is more than doubled by the presence of DMF. These synergisms clearly depend on the presence of cavitation as confirmed by subharmonic detection. To consistently create acoustic cavitation, the authors introduced albumin stabilized microbubbles into the exposure chamber. These microbubbles, similar to those used as ultrasound contrast agents, serve as cavitation nuclei and improve prospects for cancer therapy using acoustic cavitation